Treatment and Prevention of Bipolar Depression – Part 2

While antidepressants are not indicated in
the treatment of bipolar depression as monotherapy, they are still commonly
prescribed. Part two of this article looks at how the International Consensus
Group viewed the evidence for antidepressant use in bipolar disorder treatment
and episode prevention.

Antidepressants appear to have a very
different risk and reward profile depending on the specific antidepressant or
antidepressant class but there aren’t enough studies for information on all
possibilities. One thing we do know, based on a 10-year study though, is that
those treated with antidepressant monotherapy had more switching to mania or
hypomania and more suicide
attempts than those who received an antidepressant with a mood stabilizer.

Antidepressant Therapy for Bipolar Depression

In one study, paroxetine (Paxil) monotherapy
was compared with quetiapine (Seoquel) monotherapy in bipolar depression.
Paroxetine was not much more effective than the placebo, while quetiapine was
more effective than both.

One study showed no clear benefit when
either paroxetine or venlafaxine (Effexor) was added to a mood stabilizer while
another study did show improvement in a very similar scenario. However, the
best evidence seems to be for adjunctive treatment with fluoxetine (Prozac). In
one study, fluoxetine combined with olanzapine (Zyprexa) more successfully
treated bipolar depression than either placebo or olanzapine alone.

(In the U.S., a fluoxetine / olanzapine
combination is available in a single medication known as Symbyax.)

It’s important to note that
serotonin-norepinephrine reuptake inhibitors like venlafaxine (Effexor) and
tricyclic antidepressants appear to have a much greater risk of mood switching
when compared to selective serotonin reuptake inhibitors (like paroxetine).

The biggest predictor of a positive
response to adjunctive antidepressant treatment was a past history of positive
response to antidepressants. Nonresponders:

had a greater number of mood
switches during prior antidepressant treatment

had a greater number of total
depressive and hypomanic episodes

The group noted that antidepressants should
not be added when any manic symptoms are present due to the increased risk of
mood switching. Patients with a history of rapid-cycling or mixed episodes are
also not good candidates for antidepressant treatment.

Long-Term Use of Antidepressants in Bipolar Disorder

Varied evidence exists on the long-term use
of antidepressants in bipolar depression treatment. In one meta-analysis,
long-term adjunctive treatment with an antidepressant showed little value over
mood stabilizer treatment alone and an (insignificant) trend towards mania was
seen. However, it should be noted that these studies are mostly old and most
often contained the use of tricyclic antidepressants, and not the newer agents.

In other studies, mood stabilizers with
antidepressants were found to increase continued remission rates by up to 100
percent when compared to mood stabilizers alone.

One of the experts of the group noted that
this more current data agreed with his clinical judgement and experience.
According to this doctor, “in those patients for whom antidepressants are effective, continuing the
antidepressant is reasonable.” Continued antidepressant use may also be
considered when a patient has a comorbidity like obsessive-compulsive disorder
or anxiety.

Overall Recommendations for the Prevention of Bipolar
Depression

The International Consensus Group ends with
10 recommendations in the prevention of bipolar depression. They are:

Quetiapine, lithium and
lamotrigine are recommended for acute depressive episodes. It’s recommended
that medications be continued from the acute stage into the maintenance stage.

Taper antidepressants in the
maintenance phase, if used, unless there is a history of relapse after
discontinuing antidepressants.

Lamotrigine is preferred for
patients with a predominance of depression, atypical depression, obesity or
medication comorbidities. Lamotrigine is not recommended for those with mixed
episodes. Lamotrigine is not recommended as monotherapy for those with
depression with psychotic features, but can be combined with an antipsychotic.
Lamotrigine is recommended for patients with a history of switching while on
antidepressant treatment.

Olanazpine and quetiapine is
preferred for patients with a predominance of mania and without obesity or
diabetes mellitus and who do not gain weight while taking the drug.

Quetiapine plus lamotrigine,
lamotrigine plus lithium, lithium plus quetiapine, or all three medications can
be used in combination.

Long-acting risperidone is
appropriate for patients with adherence issues, but patients should be
monitored for prolactin side effects.

Valproate may be effective for
maintenance treatment of bipolar disorder.

Healthline’s mission is to make the people of the world healthier through the power of information. We do this by creating quality health information that is authoritative, approachable, and actionable.

Join more than 30 million monthly visitors like you and let Healthline be your guide to better health.